The coordination of neurogenesis and differentiation in development is important for the formation of precise neuronal circuitry. Recent studies have provided evidence that axonal interaction with target tissue can regulate neurogenesis. The specific aims of this application are designed to examine the mechanisms by which olfactory axons interact with the developing telencephalon to regulate neurogenesis in the olfactory bulb primordium that develops from the rostral end of the telencephalon. We will use in vitro experimental approaches and combine these with cell cycle kinetics analysis. The major experimental goals are to: 1) examine the role of the early olfactory axons in regulating cell cycle kinetics in the olfactory bulb primordium; 2) investigate whether the early olfactory axons play a role in determining whether neurons in the olfactory bulb primordium become mitral cells; and 3) determine whether the pioneer olfactory axons are unique in their ability to regulate the morphogenesis of the olfactory bulb. The long-term goals of this work are to elucidate the roles of extrinsic signals in regulating mechanisms of neural production in CNS, with a focus on the olfactory bulb. We expect that evidence obtained through this study will provide insights into how the cell cycles of CNS cells are regulated. The determination of critical regulatory steps during cytogenesis will facilitate further analysis of the molecular players involved in this process.